Social stress and inflammatory processes are strong regulators of one another. Considerable evidence shows that social threats trigger inflammatory responses that increase infection susceptibility in both humans and animals, while infectious disease triggers inflammation that in turn regulates social behaviours. However, no previous study has examined whether young children's popularity and their rate of infectious disease are associated. We investigated the longitudinal bidirectional links between children's popularity status as perceived by peers, and parent reports of a variety of infectious diseases that are common in early childhood (i.e. common cold as well as eye, ear, throat, lung and gastric infections). We used data from the 'Matter of the First Friendship Study' (MOFF), a longitudinal prospective multi-informant study, following 579 Norwegian pre-schoolers (292 girls, median age at baseline = six years) with annual assessments over a period of three years. Social network analysis was used to estimate each child's level of popularity. Cross-lagged autoregressive analyses revealed negative dose-response relations between children's popularity scores and subsequent infection (b = -0.18, CI = -0.29, -0.06, and b = -0.13, CI = -0.23, -0.03). In conclusion, the results suggest that children who are unpopular in early childhood are at increased risk of contracting infection the following year.